AMES, Iowa - A researcher at Iowa State University has
discovered how a group of proteins from plant pathogenic
bacteria interact with DNA in the plant cell, opening up the
possibility for what the scientist calls a "cascade of
advances."

Adam Bogdanove, associate professor in plant pathology, was
researching the molecular basis of bacterial diseases of rice
when he and Matthew Moscou, a student in the bioinformatics and
computation biology graduate program, discovered that the
so-called TAL effector proteins injected into plant cells by
strains of the bacterium Xanthomonas attach at specific
locations to host DNA molecules.

They found that different proteins of this class bind to
different DNA locations, and particular amino acids in each
protein determine those locations, called binding sites, in a
very straightforward way.

"When we hit on it, we thought, 'Wow, this is so
simple, it's ridiculous,'" Bogdanove said.

Bogdanove's research will be published in an upcoming issue
of the journal Science and is highlighted in last week's
Science Express, an early online edition for research the
Science editors feel is particularly timely and important. The
paper is being published alongside a study from another
research team that arrived at the same conclusions
independently.

In his research, Bogdanove was examining how Xanthomonas uses
TAL effectors to manipulate gene function in plants in ways
that benefit the pathogen. Bogdanove was specifically
interested in how different TAL effector proteins are able to
activate different corresponding plant genes.

Over the past decade, understanding of this unique class of
proteins has grown in leaps and bounds, according to Bogdanove.

Researchers in Germany, at Kansas State University, Manhattan;
and here at Iowa State (Bing Yang, assistant professor in
genetics development and cell biology) had previously shown
that these proteins bind host DNA and activate genes important
for disease, or in some cases defense against the bacteria. But
no one yet understood how different TAL effectors recognized
different parts of the DNA in order to attach and turn on the
different genes at those locations.

Through computer analyses, Bogdanove and Moscou discovered that
pairs of amino acids distributed throughout a TAL effector
protein each specify a particular nucleotide, one of the bases
in DNA abbreviated as the letters G, A, T, or C. The complete
set of these pairs directs the protein to a matching string of
Gs, As, Ts, and Cs in the DNA.

"This simple relationship allows us to predict where a TAL
effector will bind, and what genes it will activate. It also
makes it likely that we can custom engineer TAL effectors to
bind to virtually any DNA sequence," says Bogdanove.

According to Bogdanove, being able to predict TAL effector
binding sites will lead quickly to the identification of plant
genes that are important in disease. Natural variants that lack
these binding sites are a potential source of disease
resistance.

Another potential application is adding TAL effector binding
sites to defense-related genes so they are activated upon
infection.

The possibilities for this new technology extend beyond plant
disease control, according to Bogdanove.

"We might be able to use TAL effectors to activate genes
in non-plant cells, possibly even in human stem cells for gene
therapy. Or we might be able to use them to modify DNA at
specific locations and help us study gene function. This could
apply in many areas, including cancer research, for
example," he said.

Bogdanove said the simplicity of the results surprised the
research team.

"A predictable and potentially customizable kind of
protein-DNA binding has been hard to find in nature. As Matt
and I talked about the possibilities, we got excited and one of
us said - I don't remember who - 'We've got to
submit this to Science, dude,'" said Bogdanove.

Moscou investigated TAL effector DNA binding with Bogdanove
through his participation in the Bioinformatics and Computation
Biology (BCB) Lab, a student-run organization that provides
assistance with computational analyses for life science
researchers on campus. Moscou is a founding member of the BCB
Lab, which is supported by a training grant to the BCB graduate
program from the National Science Foundation. Moscou is doing
his dissertation research on a plant pathogenic fungus under
Roger Wise, professor in plant pathology.

Research in the Bogdanove laboratory is supported by funding
from the NSF Plant Genome Research Program and from the United
Stated Department of Agriculture - Agricultural and Food
Research Initiative program.

Contacts

Adam Bogdanove, Plant Pathology, (515) 294-3421,
ajbog@iastate.edu

Dan Kuester, News Service, 515-294-0704,
kuester@iastate.edu

Quote

When we hit on it, we thought, 'Wow, this is so simple,
it's ridiculous.'

Adam Bogdanove

Quick Look

Adam Bogdanove, associate professor in plant pathology, was
researching the molecular basis of bacterial diseases of rice
when he discovered how a group of proteins from plant
pathogenic bacteria interact with DNA in the plant cell,
opening up the possibility for what the scientist calls a
"cascade of advances."